Fake Blood? This Is a Hospital NOT a Horror Movie

Yesterday, New Scientist broke the story about a company, known as HemoBiotech which has come up with a more realistic form of fake blood, called HemoTech. I don't mean that they've finally realised that cherryade is too pink for use in movies. No, I mean fake blood that can keep people alive. Vampires around the globe are now at the edge of their seats (or coffins..or whatever..who cares, they don't really exist)

The companies claims about their product seem really quite impressive. They've just submitted a patent application for their product and they are hoping to start trials on it soon.What is Fake Blood and Why Do we Need It ?In our bodies, we need blood mainly to transport oxygen to the living cells of our bodies, and remove carbon-dioxides and other waste gases from our cells. This is done by red blood cells which contain haemoglobin, and this binds to oxygen and transports it to our body cells.When a person has an accident, a lot of blood is lost, and so there are a lot of cells in the body which end up needing oxygen. If circulation isn't replaced, the body's cells can end up dying off. This is why , during accidents, and in some traumatic surgical operations, people need blood transfusions. However, not every blood group is compatible, and immune reactions can occur in which the transfused blood can be rejected, leading to a systemic inflammatory response (which is not good)However, if you could develop a hypoallergenic fake blood substitute which performs all the same functions as red blood cells. However, this fake blood cannot be a replacement, as blood has multiple other functions which need to be performed on a longer term basis. This is only a short term treatment.A Short History of Blood transfusionsPeople have been experimenting with replacing blood for over a century. Animal to human blood transfusions have been attempted since the sixteenth century. Sir Christopher Wren suggested that ale, wine and opiates should be used as a substitute for blood (he may have ended up killing his patients, but they were a lot more happy) Animal transfusions were also performed, but ended up being banned in 1677 1878 is when the first successful human-to-human transfusions occurred (with a 50% success rate). if you want to read more about this, look hereTypes of Fake BloodHaemoglobin protein Normal red blood cells which transport oxygen to the body are packed with haemoglobin- this is the molecule which actually binds to and carries the oxygen. So the most logical step for creating fake blood would be to use this as a substitute. Amberson carried out investigations into this in the 1930's, and managed to keep his lab animals alive for 36 hours.[2] He soon moved on to trying it out on human patients with some success[3]. That is, he cured the disease he treated his patients for. One of the problems with using haemoglobin protein on it's own is that it is toxic to the kidneys. haemoglobin is usually only kept in red blood cells, and it isn't leaked out into the bloodstream usually. This means that the blood cells , and the haemoglobin molecules within them, are disposed of in the spleen (yes that's what your spleen is for). However, when haemoglobin molecules are on their own, they can end up in the kidneys, where they can cause severe damage. Not only that, but haemoglobin on its own can also cause the build up of superoxide radicals, and it can dissolve in the blood vessel walls to cause over-oxygenation. In response to this , the blood vessels constrict, causing hypertension. So there is a great need to make haemoglobin molecules less toxicThis is done by taking a bunch of haemoglobin molecules and joining them up to form a large bundle, which prevents them going out of control. This in itself is quite difficult, because by joining up haemoglobin molecules, you change their properties, and make it so that they don't bind the blood as well. However, this problem has been solved, and there have been animal trials in which artificial blood has kept animals alive for several days [4]There are several haemoglobin-based blood substitutes in development.Hemopure: This product was developed by biopure, and is based on cow haemoglobin. It has been registered in South Africa for the treatment of clinical anaemia. It has shown positive results here, but there are some side effects.PolyHeme and Hemalink are other blood products on the market which have also produced trials, albeit with slightly mixed results. Generally, they "Do what they say on the tin", they work as blood substitutes. But there are worries about side effects. (Hemalink may have caused heart problems in a clinical trial, Patients treated with PolyHeme seemed to do worse than patients treated with saline in one trial)However, the main problem at the moment with these is that they are incredibly hard to produce. Extracting haemoglobin from blood donor cells, and then crosslinking it costs a lot of time energy and money.Liposome Encapsulated HaemoglobinLiposomes are small spheres constructed out of lipids. these can be used as carriers for haemoglobin. the advantages of these are that they don't have any blood group antigens to elicit an immune response, and they can be used as haemoglobin carriers, and thus prevent haemoglobin toxicity associated with the other treatments mentioned above.However, the main problem here is that this technology is still in very early stages, and development has been difficult. For a start, its been difficult getting the size of the liposomes correct, in order to make sure they don't get trapped in capillaries. There have been successful experiments in lab animals demonstrating the oxygen carrying capability of these constructs [5], but the research is seems to be a long time away from human trials, and pharmaceutical companies have not yet jumped on this bandwagon. Possibly it could be that with this treatment, you are taking the already expensive haemoglobin extraction process, and then getting it packaged into liposomes to industry quality.PerfluorocarbonsExperiments with perfluorocarbons as oxygen carriers started in the 60's. Perfluorocarbons are good, because they are less poisonous than using pure haemoglobin, and cheaper to manufacture.Also, they are able to bind to a lot of oxygen to the extent that it is possible for animals to survive if they are completely submersed in perfluorocarbon[1]. The perfluorocarbons are also good because they are readily excreted through the lungs- you end up breathing it out. So it is a relatively safe treatment. however, there are some problems with it:

They are not soluble with the blood, and therefore not bioavailable. the only way to get it to work would be to introduce emulsifying agents.

They can cause inflammation, although this has been linked to the emulsifying agents which they have been administered alongside.

The Excretion pathways for these products has not been fully mapped out. while we know that they can be excreted safely out of the lungs, it is possible that some of the metabolism occurs in the liver. in some animals exposed to these products, the Liver and the Spleen have been seen to expand, and they produce more enzymes. This could mean that they are toxic.

These perfluorocarbons are not as good as haemoglobin at absorbing oxygen (if they were better at grabbing oxygen than haemoglobin, immersing a rat in a bath of perfluorocarbon would cause it to have the oxygen sucked out of it's blood cells, rather than sucked in) Patients undergoing this treatment have to breath pure oxygen in order for the treatment to be effective.

So these are the products that are in development at the moment. The question is, what does HemoTech add to the mix that makes it better than all of it's predecessors?HemoBiotech are offering a Crosslinked Bovine Haemoglobin based treatment, similar to the HemoPure treatment which is arguably one of the more successful blood replacement products.The advantages of using bovine haemoglobin is that there is a ready supply. If there was enough human haemoglobin available, we wouldn't need blood substitutes.However, where Hemotech differs from previous Haemoglobin treatments is that it has conjugated anti-inflammatory signals with it's haemoglobin. This is a direct effort to counter-act the toxic side effects encountered by other drugs. it is conjugated with glutathione and adenosine, both of which have anti-inflammatory , and more importantly vasodilatory effects, so hypertension should not (theoretically) be a side effect. HemoBiotech's Jan Simoni has spent some time studying the effects of haemoglobin on the circulatory system [6] and essentially identified that the main "nemesis of blood substitute developers" is the vasoconstriction effect.So on paper, it seems that this could end up being a successful treatment. However, I would be very cautious about a product like this before a clinical trial.This is mainly because for a clinical trial, there are often side effects that pop up that no-one expects. Putting an anti-inflammatory component could be a great idea, and it could work perfectly, and Nobel prizes and big cigars will be handed out. But then again, it may not be a great idea. What is being marketed is not a non-inflammatory version of fake blood, but an anti-inflammatory edition. The idea behind it is not to avoid a reaction altogether, but to counteract any inflammatory reaction enough so that there is no visible effect. This means that any anti-inflammatory, or indeed pro-inflammatory drugs, will be affected by the artificial blood in the patients blood stream. If you are looking at major blood replacement, this dose of anti-inflammatory could be EXTREMELY high. this is all complicated by the fact that regulatory authorities also have to account for athletes obtaining samples of fake blood, and using them to enhance their performance in competitions. If that fake blood is toxic, you may as well be giving out poison (which is NOT ethical).Imagine you are on a life boat and suddenly it springs a leak. You stick your thumb in that leak, and two more pop up. This is what I imagine it's like for people developing fake blood. They get one problem solved, and two or three more pop up. So if I were you, i wouldn't wait for scientists to come up with a fake blood solution. Go out and Donate Blood. Seriously.